Patent Evaluation: Substituted Cephalosporins as Antibacterial Agents

Summary

Novelty: 3-Arylpropenyl substituted cephalosporin derivatives are disclosed. They are potentially useful antibacterial agents.

Biology: Minimum inhibitory concentrations of the compounds are presented against a variety of organisms including penicillin and cephalothin resistant strains. MIC values range from 0.1–10.0 μg/ml for selected compounds against sensitive and resistant strains of Straphylococcus aureus and Klebsiella pneumoniae. Selected compounds were also shown to be effective in vivo against S. aureus, E. coli and P. aeruginosa with PD₅₀ values of between 0.3–0.6 mg/kg im

Chemistry: Preparation of the compounds is outlined in two synthetic schemes and exemplified in fifty cases which form a subsidiary part of the claim. A biologically active compound is 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[(E)-3-(5,6-dihydroxy-2-methyl-2-isoindolino)-1-propen-1-yl]-3-cephem-4-carboxylate.

Structure: